Effects of Fluorodeoxyuridine on Age Changes in Caenorhabditis Elegans
Effects of fluorodeoxyuridine on age changes in Caenorhabditis elegans
Ruxandra-Maria Comisel 1, Jennifer Tullet 1, Marina Ezcurra 1, David Gems 1
1
Institute of Healthy Ageing, and G.E.E., University College London, Darwin Building,
Gower Street, London WC1E 6BT, UK
Yolk in C. elegans exists as lipoprotein-like particles composed of lipids and lipid binding vitellogenin proteins.
It is transported from the intestine, site of synthesis, to the
oocytes, and accumulates with age in post-reproductive nematodes. Fluorodeoxyuridine
(FUdR), a DNA-synthesis inhibitor known to block progeny production, was used in an investigation of yolk venting behaviour in ageing animals. In this study, it was serendipitously found that 10 µM FUdR affected lipid levels and this was pursued.
Microscopy showed that FUdR lowers lipid pool size. A reduction in fat content was biochemically confirmed by measurement of triglyceride levels. This and the electrophoretic analysis of vitellogenins implied a deceleration of the age increase in yolk fat and protein levels in FUdR treated nematodes. The possibility that this result was due to FUdR altering the intestine size was excluded by measurements of intestinal diameter. That yolk protein levels were reduced in FUdR treated animals, suggested that FUdR may influence transcription. Lowered fat content could also reflect the FUdR effects on transcription of fat metabolism enzymes. Alternatively, FUdR, inhibitor of thymidylate synthetase, might reduce lipogenesis through interference in the folate metabolism. These results have the potential to contribute to the growing concern over the use of FUdR in lifespan studies as they show that this chemical impacts fat levels, perhaps through transcription and/or folate metabolism in C. elegans.
Ruxandra-Maria Comisel 1, Jennifer Tullet 1, Marina Ezcurra 1, David Gems 1
1
Institute of Healthy Ageing, and G.E.E., University College London, Darwin Building,
Gower Street, London WC1E 6BT, UK
Yolk in C. elegans exists as lipoprotein-like particles composed of lipids and lipid binding vitellogenin proteins.
It is transported from the intestine, site of synthesis, to the
oocytes, and accumulates with age in post-reproductive nematodes. Fluorodeoxyuridine
(FUdR), a DNA-synthesis inhibitor known to block progeny production, was used in an investigation of yolk venting behaviour in ageing animals. In this study, it was serendipitously found that 10 µM FUdR affected lipid levels and this was pursued.
Microscopy showed that FUdR lowers lipid pool size. A reduction in fat content was biochemically confirmed by measurement of triglyceride levels. This and the electrophoretic analysis of vitellogenins implied a deceleration of the age increase in yolk fat and protein levels in FUdR treated nematodes. The possibility that this result was due to FUdR altering the intestine size was excluded by measurements of intestinal diameter. That yolk protein levels were reduced in FUdR treated animals, suggested that FUdR may influence transcription. Lowered fat content could also reflect the FUdR effects on transcription of fat metabolism enzymes. Alternatively, FUdR, inhibitor of thymidylate synthetase, might reduce lipogenesis through interference in the folate metabolism. These results have the potential to contribute to the growing concern over the use of FUdR in lifespan studies as they show that this chemical impacts fat levels, perhaps through transcription and/or folate metabolism in C. elegans.